Project Summary/Abstract: Gestational diabetes mellitus (GDM) is associated with significant perinatal morbidity, fetal growth abnormalities and in the development of Type 2 diabetes later in life in affected offspring. We have recently demonstrated that severe periodontal infection is increased in gestational diabetics compared to non-diabetic Asian and Pacific Islander (API) women. Since API women are disproportionately affected by GDM, we have the unique opportunity to study the mechanisms underlying the documented association between oral infection and GDM in a high risk cohort. Our specific aims are: (1) to determine whether fetal-placental exposure to maternal oral organisms is associated with a decrease in insulin-like growth factor-2 (IGF2) in maternal serum and/or fetal cord blood at delivery and to demonstrate fetal IgM seropositivity and IGF2 suppression are intermediary explanatory variables in the association between maternal periodontal status and glycemic control; (2) to determine whether maternal periodontal disease is associated with a decrease in the level of IGF1 in maternal serum and to demonstrate IGF1 suppression is an intermediary variable in the association between maternal periodontal status and glycemic control; and (3) to establish necessary infrastructure and support to conduct a longitudinal clinical trial from < 16 weeks gestational age until 3 months postpartum. A cohort of 200 pregnant API women will be recruited and followed to determine the association between periodontal disease, IGF1, IGF2, and glycemic control. Data collection will include: demographics, antepartum care, labor, delivery, and neonatal outcomes, and glycemic control. Interviews and periodontal exams will be performed at baseline, at delivery, and at 3 months postpartum. Maternal blood will be obtained for glucose and IGF1 assays. Fetal cord blood samples will measure IGF2 and IgM levels to 18 oral microbes. Maternal blood, fetal cord blood, plaque, and placental samples will be stored for additional assays, if indicated. We anticipate our investigation will demonstrate IGF1 and IGF2 are decreased in women with moderate-severe periodontal disease and impaired glycemic control. This pilot project will additionally enable us to establish the infrastructure to conduct a large longitudinal clinical trial designed to demonstrate that periodontal disease increases the incidence and severity of GDM and persistence of insulin resistance postpartum; and to further study the mechanism of that effect. Narrative We hypothesize that periodontal disease associated inflammatory stressors contribute to insulin resistance through a fundamental alteration in the maternal-fetal IGF (insulin-like growth factor) axis. [unreadable] [unreadable] [unreadable]